لال بہادر شاستری
پنڈت جواہر لال نہرو کا غم ابھی فراموش نہ ہوا تھا کہ ملک نے ایک اور لعل بے بہا کھودیا، شری لال بہادر شاستری کی موت ہندوستان کا عظیم ترین حادثہ ہے۔ ان کی موت سے ہندوستان ایک ایسے فرزند سے محروم ہوگیا جس کی تلافی مدتوں نہ ہوسکے گی، انھوں نے ملک و قوم کی خاطر غریب الوطنی میں جان دی اور مرنے سے پہلے ایک ایسا کارنامہ انجام دے گئے جو ہند و پاک کی تاریخ میں یادگار رہے گا، مگر افسوس کہ اس کے خوشگوار نتائج اپنی آنکھوں سے نہ دیکھ سکے، پنڈت جواہر لال نہرو کی زندگی ہی میں یہ سوال پیدا ہوگیا تھا کہ ان کے بعد کوئی ایسی شخصیت نظر نہیں آتی جو وزارت عظمیٰ کے بارگراں کو سنبھال سکے، لیکن شاستری جی نے اٹھارہ مہینہ کی مختصر مدت میں یہ ثابت کردیا کہ وہ پنڈت جی کے صحیح جانشین تھے۔ اس قلیل مدت میں بڑے پیچیدہ اور نازک معاملات پیش آئے، لیکن شاستری جی نے اپنے فہم و تدبر اور ہمت و پامردی سے ان کا پورا مقابلہ کیا، معاہدہ تاشقند تو ان کے اور جنرل ایوب کے تدبر کا شاہکار ہے، گو اس سے سب مختلف فیہ مسائل حل نہیں ہوگئے، لیکن ہندوستان اور پاکستان کی ہلاکت خیز جنگ کا خاتمہ ہوگیا، اور صلح و مسالمت کی ایسی فضا پیدا ہوگئی ہے کہ اگر فریقین نے ہوشمندی سے کام لیا تو ہندوستان و پاکستان کے درمیان مصالحت اور دوستی کا خوشگوار دور شروع ہوسکتا ہے۔
شاستری جی بڑے ٹھنڈے دل و دماغ کے اور طبعاً نرم مزاج، صلح جو اور امن پسند انسان تھے، لیکن سختی کے موقع پر سخت اور ہمت و استقلال کا پیکر بن جاتے تھے، انھوں ے اپنی سلامت روی اور ہوشمندی سے ملک کو بڑے نازک حالات سے نکالا، افسوس ہے...
Until recently, Gwadar has always been mentioned as a small insignificant fishing town. Very little was known about its history and potential to the outside world. However, at the turn of the 21st century Gwadar became the focus of attention globally. The development of a deep seaport with China’s assistance and prospects of connecting China and Central Asia through Pakistan to the North Arabian Sea has brought this small, insignificant fishing town to international recognition. But history reveals that this region has always played a vital role since primeval times due to its geostrategic and geographical location. From Alexander’s retreat to Pakistan’s reclaiming Gwadar, it has always reminded its significance at different times in diverse manners. This paper aims to bring into light the historical journey of Gwadar, which usually remained unknown or were either considered trivial by historians. Gwadar became an important chapter in the Belt and Road initiative proposed by the Chinese president. It will link China, South Asia, Middle East, Central Asia, Africa and Europe through a network of land and sea routes and ports will contribute significantly to the progress and prosperity of Gwadar in Pakistan, China and the entire region.
The Khyber Pakhtunkhwa region of Pakistan has been known for a high burden of tuberculosis (TB). However, there is little information about the molecular characteristics of Mycobacterium tuberculosis (M. tuberculosis) strains predominant in the province. Therefore, this study was planned to study the genetic diversity and molecular patterns responsible for the extensive drug resistance in the M. tuberculosis isolates isolated from clinical samples. In the current study total 794 patients were tested for suspected tuberculosis by fluorescence microscopy and GeneXpert system at the Provincial TB Reference Laboratory, Khyber Pakhtunkhwa, Pakistan. Among the 794 patients studied, 170 samples gave positive results and were further tested for drug susceptibility, out of which 163 samples gave results of drug susceptibility test. Among these 163 isolates, 79 (48.46%) were resistant to isoniazid, 47 (28.83%) were resistant to streptomycin, 56 (34.35%) were resistant to rifampicin, 31 (19.01%) were resistant to ethambutol, 16 (9.81%) were resistant to pyrazinamide, 59 (36.1%) were resistant to ofloxacin, 12 (7.36%) were resistant to capreomycin and 11 (6.74%) were resistant to amikacin. Further, these resistant isolates were selected for mutation analysis in the ‘hot spot regions’ of katG, rpoB, inhA, rpsL, embB, pncA, gyrA and gyrB genes. For the mutation analysis of the hotspot regions of katG and inhA genes, 30 resistant isolates were selected randomly. Among these 30 isolates, 21 (70%) had a mutation in katG gene and two (6.6%) had the most common C15T mutation in inhA promoter region. In 21 katG mutant isolates, 15 showed Ser315Thr, three showed Gly316Ser, two showed Ser315Arg mutations while one isolate was positive for a double mutation of Ser303Trp and Lys274Arg. Fourteen isolates were analyzed for the rpoB gene mutation. The mutations detected in rpoB gene in the selected isolates were Ser450Leu, Asp435Gly, Ser450Gln, Gly455Asp and Pro454His. Sixteen isolates were analyzed for streptomycin resistant-mutation in the rpsL gene. The rpsL gene mutations detected in six isolates were Lys43Arg, Lys88Arg, and Lys111Ile. Sixteen isolates were analyzed for ethambutol resistant-mutations of the embB gene. Out of these, 10 isolates were positive for Ala281val, Met306Leu, and Met306Val mutations. Eight isolates were analyzed for pyrazinamide resistant mutations of the pncA gene. Among them, 5 isolates showed a mutation in pncA gene, which included Gln141Pro, Ser65Ser*, Gly132Ser and Cys138stop mutations. The insertion of G at position 392 was also detected in pncA gene. Twenty isolates were analyzed for ofloxacin resistant mutations in gyrA and gyrB genes. Asp94Gly mutation in gyrA gene was detected in nine isolates while no mutation for the gyrB gene was detected in the selected isolates. These findings provide insights into the genetic variability existing against various drugs in M. tuberculosis circulating in Khyber Pakhtunkhwa, Pakistan. The results showed some novel mutations in the genes, katG, rpoB, rpsL and pncA. Small molecule inhibitors of the proteins encoded by the drug resistant genes, i.e., KatG, gyrA, pncA and rpoB of M. tuberculosis, were identified using computational methods. On the basis of the docking score and binding interactions, ten small molecule compounds were identified as novel inhibitors of each protein. These compounds showed significant interaction with the active site of the protein. The genetic diversity of M. tuberculosis isolates was estimated using RAPD and PCR restriction enzyme analysis.Fifty-two MTBC isolates were randomly selected for RAPD-PCR and PCR-restriction enzyme analysis. M. Bovis and M. tuberculosis H37Rv were used as reference strains. RAPD-PCR differentiated the strains and authenticated the high molecular diversity.PCR restriction enzyme analysis (PRA) profiles of all isolates and reference strains were found to be the same. High diversity values were found in the studied area implying high population diversity of M. tuberculosis that’s being prevalent in Khyber Pakhtunkhwa, Pakistan. The development of M. tuberculosis resistant strains is a major challenge severely affecting public health worldwide. New drugs obtained from natural resources could be a viable option to avoid serious drug resistance issues. On this quest, Aspergillus and Penicillium spp. were isolated from the surface soil. The secondary metabolites of Aspergillus and Penicillium were screened for anti-tuberculosis activity. The secondary metabolites of Aspergillus were active against M. tuberculosis whereas those of Penicillium showed no significant inhibitory activity. The results provide an overview of the existing nature of Multi drug resistance in M. tuberculosis circulating in Khyber Pakhtunkhwa province of Pakistan.